Using chronic dogs with gastric fistula and silastic catheter in the splenic vein after splenectomy ex vivo prostaglandin generation will be measured in biopsy material from the gastric mucosa via a gastroscope, and close gastric venous blood can be obtained for assay by radioimmunoassay of prostaglandin and thromboxane concentrations. Does response relationships will be determined between a range of aspirin and indomethacin doses and mucosal PG generation.Dose response relationships between doses of aspirin and indomethacin which reduce PG generation 25%, 50% and 100% and visual (by endoscopy) and histologic mucosal injury will be determined. Dose response relationships between drugs which afford mucosal protection (mild irritants, carbenoxolone, cimetidine, colloidal bismuth and sucralfate) and potential increases in mucosal PG generation and/or increases in gastric venous prostaglandin concentration will be determined. Using doses of aspirin and indomethacin which reduce PG generation 25%, 50% and 100%, the effect of such doses on basal mucosal blood flow will be measured by 14C aminopyrine clearance technique to determine the degree to which endogenous PGs contribute to basal mucosal blood flow. Fluid secretion will be stimulated by histamine, gastrin, urecholine, and a meal, PG generation and gastric venous prostaglandin concentration will be measured. Increases in either parameter under these conditions will suggest that endogenous prostaglandin activity is important in the mediation of mucosal blood flow increase during stimulated acid secretion. Gastric bicarbonate secretion will be stimulated by glucagon and cholecystokinin and measured by intragastric titration. Gastric mucosal PG generation and gastric venous prostaglandin concentrations will be measured. Increases in either or both of these parameters under the conditions of this study will suggest a mediatory role by endogenous prostaglandins in glucagon and cholecystokinin-induced bicarbonate secretion.